Single‐Dose Pharmacokinetics and Safety of Atogepant in Adults With Hepatic Impairment: Results From an Open‐Label, Phase 1 Trial

Abstract Atogepant is a selective oral calcitonin gene‐related peptide receptor antagonist in development for migraine prevention. Here, we report the pharmacokinetics (PK) and safety of single‐dose 60 mg atogepant in participants with severe, moderate, or mild hepatic impairment and matched participants with normal hepatic function from an open‐label, parallel‐group, single‐dose phase 1 trial. Thirty‐two participants aged 45 to 72 years were enrolled, which included 8 each with severe, moderate, mild, or no hepatic impairment. All participants completed the study. Atogepant was rapidly absorbed (median time to maximum plasma concentration, ∼2 hours) with an apparent terminal elimination half‐life of ∼11 hours. Compared with participants with normal hepatic function, the change in maximum plasma concentrations of atogepant were –4%, –12%, and +9% in participants with severe, moderate, or mild hepatic impairment, respectively. Overall systemic exposures to atogepant were 15% to 38% higher in participants with hepatic impairment compared with those with normal hepatic function, but these differences are not expected to be clinically relevant given the established safety profile of atogepant. Only 1 adverse event was reported: mild rhinorrhea in a participant with moderate hepatic impairment. Overall, atogepant was safe and not associated with any clinically relevant change in PK in participants with severe, moderate, or mild hepatic impairment.